Risk of Arterial Thromboembolic Events With Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials

PurposeSunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib.Patients and MethodsPubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies.ResultsA total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed.ConclusionTreatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs.

Download Full-text

A comparison of drug resistances of targeted drugs for advanced renal cell cancer approved by the Food and Drug Administration: A meta-analysis of randomized clinical trials

Journal of Cancer Research and Therapeutics ◽

10.4103/0973-1482.191617 ◽

2016 ◽

Vol 12 (5) ◽

pp. 109

Author(s):

Jingfeng Zhang ◽

Ming Guo ◽

Yunsong Cao ◽

Jingzhe Yang

Keyword(s):

Clinical Trials ◽

Drug Administration ◽

Renal Cell Cancer ◽

Renal Cell ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Food And Drug Administration ◽

Cell Cancer ◽

Targeted Drugs ◽

Advanced Renal Cell Cancer

Download Full-text

Risk of arterial thromboembolic events (ATEs) with tyrosine kinase inhibitors (TKIs) used in renal cell carcinoma: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13119 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13119-e13119

Author(s):

Muhammad Zain Farooq ◽

Jessey Mathew ◽

Saad Malik ◽

V V Pavan Kedar Mukthinuthalapati ◽

Noureen Asghar ◽

...

Keyword(s):

Systematic Review ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Meta Analysis ◽

Thromboembolic Events ◽

Phase 2 ◽

Open Label ◽

Increased Risk ◽

Arterial Thromboembolic Events

e13119 Background: Tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of metastatic RCC and Sunitinib is approved for the use in adjuvant setting. Arterial thromboembolic events (ATEs) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence associated with the use of FDA approved TKIs used in treatment of RCC. Methods: PubMed, EMBASE, Cochrane Central and Scopus databases were searched to identify phase 2 and 3 RCTs of TKI therapy in RCC. Trials were included if they reported ATEs defined as arterial thrombosis, cerebral ischemia or infarction, myocardial ischemia and myocardial infarction. The DerSimonian-Laird random effects meta-analysis was performed using CMAv3 software to derive pooled estimates of incidence rates of ATEs with its 95% confidence interval (CI). I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: 1755 studies retrieved in the initial search, and 13 phase 2 and 3 clinical trials (n = 4983) were included in the quantitative analysis. The trials had open label design which can potentially result in bias. Risk of bias was low in all other domains. TKIs used for the treatment of RCC included sunitinib (n = 2632), sorafenib (n = 981), cabozantinib (n = 78), pazopanib (n = 844), axitinib (n = 189) and tivozanib (n = 259). The incidence of ATEs with the use of TKIs was 2.9% (95% CI: 2-3%). Cabozantinib was associated with the highest rate of ATEs (11.5%, 95% CI: 6-21%), followed by sunitinib (2.6%, 95% CI:2-3%) pazopanib (2.6%, 95% CI:2-4%) and axitinib (2.1%, 95% CI: 1-6%). The TKI with lowest event rate of ATE was tivozanib (0.8%, 95% CI:0.2-3%). Conclusions: The use of TKIs is associated with increased risk of developing ATEs. Clinicians should be aware of the possibility of increased ATEs and counsel the patients about this increased risk to enhance the process of informed decision making.

Download Full-text